We propose to investigate several lifestyle and genetic factors in relation to age-related macular degeneration (AMD) and primary open angle glaucoma (POAG) in two prospectively followed cohorts of women and men. Specifically, we will evaluate dietary intake of antioxidants and fat (including specific types of fat), postmenopausal hormone use and variants in the ATP-binding cassette-transporter retina (ABCR) gene in relation to both wet and dry AMD, and antioxidant intake, smoking, and systemic blood pressure in relation to POAG. The Nurses' Health Study (NHS) began in 1976 among 121,700 women ages 30-55 at that time. About 89,000 participants completed an extensively validated semiquantitative food frequency questionnaire (FFQ) in 1980 and every 2-4 years since. The Health Professionals Follow-up Study (HPFS) began in 1986 among 52,000 men ages 45-75, all of whom completed a FFQ at baseline and every four years since. Both groups have been sent a questionnaire biennially to update exposure information and reports of major illnesses, including AMD and POAG. Information has been collected repeatedly on specific vitamin supplement use, smoking, diagnosis of hypertension, reported blood pressure, and postmenopausal hormone use among other factors. Over 32,000 blood samples were collected in the NHS in 1989-90 and over 18,000 in the HPFS in 1993. In the proposed study we will confirm reports of AMD and POAG by contacting the participant's ophthalmologist, and obtaining detailed information from the optical record, including fundus photographs for those with AMD. A case will be considered to have AMD if it is judged to be sufficient to result in a visual acuity loss of at least 20/30 and is confirmed by a standardized review of the fundus photograph; wet and dry types will be carefully delineated by photographic review. A case will be considered to have POAG if confirmed by medical record review and is documented to have visual field loss. We anticipate 554 cases of exudative and 833 cases of dry AMD, and 1049 cases of POAG. Stratified and multivariate techniques will be used to quantify the risk of AMD and POAG according to the level of exposure after controlling for potentially important confounders; analyses will be conducted among participants who reported having a recent eye exam. Overall, the prospective design, large size of the cohorts, the high follow-up rates, repeated exposure measures, and carefully confirmed disease definitions provide a unique opportunity to evaluate several hypotheses of public health importance.